Long-Term Prostate-Specific Antigen Response on a Low-Dose Cabazitaxel Regimen for Metastatic Castration-Resistant Prostate Cancer: A Case Report

Abstract

Patient: Male, 71-year-old Final Diagnosis: Castration-resistant prostate cancer Symptoms: None Medication:— Clinical Procedure: Chemotherapy Specialty: Urology Objective: Unusual clinical course Background: Cabazitaxel is a second-generation taxane approved for patients with metastatic castration-resistant prostate cancer (CRPC). Although cabazitaxel improves overall survival when used following docetaxel chemotherapy, duration of the clinical response is relatively short, and few patients achieve a long-term response. Case Report: A 71-year-old man with prostate adenocarcinoma with an initial prostate-specific antigen (PSA) level of 4956 ng/ml, Gleason score 4+5 and cTxN0M1b was referred to our department for treatment. Several therapeutic approaches, including androgen deprivation therapy, with a combination of bicalutamide and a luteinizing hormone-releasing hormone analogue, and 4 sequential hormonal therapies including flutamide, estramustine, enzalutamide, and abiraterone, all failed to prevent disease progression. Subsequently, after 5 cycles of docetaxel chemotherapy were also ineffective, cabazitaxel chemotherapy at a dose of 20 mg/m 2 together with prednisone and pegfilgrastim was initiated. The patient developed grade 4 thrombocytopenia during the first 4 cycles, and the dosage of cabazitaxel had to be tapered to 12.5 mg/m 2 by the fifth cycle. In subsequent cycles, the treatment was continued without grade 4 thrombocytopenia or any other toxicities ≥grade 3. The patient achieved a long-term clinical response over 4 years and his PSA level continued to decrease, from 29.8 ng/ml at treatment initiation to a nadir of 2.0 ng/ml after the 60 th cycle. Conclusions: The present case is a rare example of a sustained response to low-dose cabazitaxel, and suggests its potential as a treatment option for metastatic CRPC patients. In our patient, this approach achieved a good clinical response with manageable toxicity over the long term.

Effective dose window for containing tumor burden under tolerable level

“…In a mouse model of ovarian cancer, MTD was found to increase the tumor volume by approximately four times, while 20% of the MTD maintains a stable tumor volume of approximately 130% of the initial volume over a period of 3 weeks 41 . Low-dose has also been found responsive over 4 years in the case study of a metastatic castration-resistant prostate cancer patient 42 . A theoretical upper bound of dose for tumor containment has been proposed in recent studies 5 , 43 .…”

“…This emphasizes the idea of personalized treatment. Though several successes with low-dose therapy in a clinical setting have been documented recently 42 , 58 , 59 , personalized dose modulation still needs effort. In the clinical setting, the deployment of our present approach could be challenged by the evolution of the tumor microenvironment and resistance.…”